Haploidentical stem cell transplant with post-transplantation cyclophosphamide and mini-dose methotrexate in children

Abstract

Background: Haploidentical stem cell transplantation (haplo-SCT) is an option for patients without human leukocyte antigen-matched related or unrelated donor. Post-transplantation cyclophosphamide (PTCy) is an effective method of graft versus host disease (GVHD) prophylaxis and permits the use of T-cell replete grafts in settings were ex vivo manipulation is not feasible. Methods: A retrospective study among patients younger than 18 years, with a history of hematologic malignancies who underwent haplo-SCT between 2012 and 2016. All patients received a preparative regimen of fludarabine, busulfan, and 400 cGy total body irradiation or melphalan. Post-transplant GvHD prophylaxis consisted either of PTCy (50 mg/kg on Days + 3 and + 4) and cyclosporine (CSA) plus mycophenolate (MMF) (15 mg/kg/dose, thrice daily, per os), or minidose methotrexate (MTX; 5 mg/m2 dose) on Days + 5, +7, +10, and + 15. Results: A +total of 52 children were included, whose median age was 9 years (interquartile range, 4.9–14; range, 1.2–17 years), and 63% were males. The most common complications were cytomegalovirus reactivation (57%) and hemorrhagic cystitis (36%). The acute GVHD prophylaxis was PTCy, CSA, and mini-dose MTX in 42 (81%) patients, and 10 (19%) patients received PTCy, CSA, and MMF. The cumulative incidence of acute GvHD II–IV, acute GvHD III–IV, and chronic GvHD were 42%, 8.5%, and 19%, respectively. Grades I–IV acute GvHD occurred in 100% of the patients who received prophylaxis with CSA and MMF, and 62% who received CSA and mini-dose MTX (p = .055). The transplant-related mortality at 100 days was 18%. The 5-year overall and event-free survival were 59% and 57%, respectively. Conclusions: Haplo-SCT with PT/Cy can be an available, safe, and feasible option for children with hematologic malignancies; meanwhile, the use of mini-dose of MTX was associated with lower rates of acute GVHD. However, our results require further support from prospective randomized studies to improve the efficacy of this prophylactic strategy.

T-Cell-Replete Versus ex vivo T-Cell-Depleted Haploidentical Haematopoietic Stem Cell Transplantation in Children With Acute Lymphoblastic Leukaemia and Other Haematological Malignancies

“…Reviewing the literature, however, some trends can be observed (see Table 2 for a summary) (9,12,14,35,41,60,74,75,78,79,95,(99)(100)(101)(102)(103). Generally, the cumulative incidence rates of severe (grade III-IV) aGvHD and overall as well as extensive cGvHD are higher in patients treated with the PTCy platform compared with those treated with ex vivo TCD (Table 1) (35,95).…”

“…Other publications report varied incidences of relapse after transplantation (between 23 and 45%), but all of these studies included multiple types of haematological malignancy and had very few ALL patients transplanted using PTCy (75)(76)(77)(78).…”

Successful engraftment of haploidentical stem cell transplant with post‐transplantation cyclophosphamide in a patient with adenosine deaminase deficiency

“…Bluetters et al demonstrated complete immune reconstitution in three patients with ADA deficiency in whom cytoreductive conditioning was used with haploidentical transplant 26 . Fischer et al published a series of cases with eight patients with SCID who were taken to haploidentical HSCT, prior depletion of T lymphocytes and in whom they used cyclosporine EV for two months post‐transplant, without evidence of subsequent severe GVHD, with adequate immune recovery 27 …”

“…Patient received prophylaxis of hepatic veno‐occlusive disease with ursodeoxycholic acid and for GVHD with cyclophosphamide (50 mg/kg day + 3 and + 4), cyclosporine (to maintain levels between 200 and 300 ng/ml initiates day + 4) and methotrexate (7.5 mg/mt 2 /doses day + 5, +7, +10 and + 15) 26 . Additionally, antimicrobial prophylaxis was conducted post‐transplant with azithromycin, acyclovir, isoniazid, and caspofungin.…”

Prophylaxis for invasive fungal infection in pediatric patients with allogeneic hematopoietic stem cell transplantation

“…The conditioning regimen was classified as myeloablative or reduced in intensity [ 22 ]. Graft-versus-host disease (GVHD) prophylaxis was performed according to the transplant type [ 23 - 25 ]. The graft was defined according to the literature [ 26 ].…”